Published Online
on February 9, 2009

A more recent version of this article appeared on February 24, 2009

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Submitted on April 10, 2008
Accepted on November 17, 2008

Effects of the Selective Estrogen Receptor Modulator Raloxifene on Coronary Outcomes in The Raloxifene Use for the Heart Trial. Results of Subgroup Analyses by Age and Other Factors

Peter Collins MD^*, Lori Mosca MD, MPH, PhD, Mary Jane Geiger MD, PhD, Deborah Grady MD, Marcel Kornitzer MD, Messan G. Amewou-Atisso PhD, Mark B. Effron MD, Sherie A. Dowsett PhD, Elizabeth Barrett-Connor MD, and Nanette K. Wenger MD

From the Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK (P.C.); Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY (L.M.); Lilly Research Laboratories, Eli Lilly and Co, Indianapolis, Ind (M.J.G., M.G.A.-A., M.B.E., S.A.D.); Departments of Medicine, University of California, San Francisco, and the San Francisco VA Medical Center, San Francisco (D.G.); Department of Epidemiology and Health Promotion, School of Public Health, Brussels Free University, Brussels, Belgium (M.K.); Departments of Family and Preventive Medicine and of Medicine, University of California–San Diego, La Jolla, Calif (E.B.-C.); and Emory University School of Medicine, Atlanta, Ga (N.K.W.).

^* To whom correspondence should be addressed. E-mail: peter.collins{at}imperial.ac.uk.

Background—The Raloxifene Use for The Heart (RUTH) trial showed that raloxifene, a selective estrogen receptor modulator, had no overall effect on the incidence of coronary events in women with established coronary heart disease or coronary heart disease risk factors. We provide detailed results of the effect of raloxifene on coronary outcomes over time and for 24 subgroups (17 predefined, 7 post hoc).

Methods and Results—Postmenopausal women (n=10 101; mean age, 67 years) were randomized to raloxifene 60 mg/d or placebo for a median of 5.6 years. Coronary outcomes were assessed by treatment group in women with coronary heart disease risk factors and those with established coronary heart disease. Raloxifene had no effect on the incidence of coronary events in any subgroup except in the case of a post hoc age subgroup analysis using age categories defined in the Women's Health Initiative randomized trials. The effect of raloxifene on the incidence of coronary events differed significantly by age (interaction P=0.0118). The incidence of coronary events in women <60 years of age was significantly lower in those assigned raloxifene (50 events) compared with placebo (84 events; hazard ratio, 0.59; 95% confidence interval, 0.41 to 0.83; P=0.003; absolute risk reduction, 36 per 1000 women treated for 1 year). No difference was found between treatment groups in the incidence of coronary events in women 60 and <70 or 70 years of age.

Conclusions—In postmenopausal women at increased risk of coronary events, the overall lack of benefit of raloxifene was similar across the prespecified subgroups.

Key words: coronary disease • hormones • raloxifene • randomized controlled trial • risk factors • women

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Clinical Summaries
Circulation 2009 119: 909-911. [Extract] [Full Text]

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